Melt extruded nicotine thin strips

Abstract

A thin strip for oral ingestion is between 0.05 millimeters and 2.00 millimeters thick. It includes 10 to 80% by weight of polyethylene oxide having a molecular weight of from 70,000 to 300,000 daltons. It further includes 5 to 50% by weight of a sugar alcohol having a melting point in excess of 75 C and 5 to 30% by weight of polyethylene glycol having a molecular weight of from 200 to 1,000 daltons. Lastly it includes 1 to 30% by weight of a carboxy vinyl polymer cross linked with an allyl ether of pentaerythritol, and 1 to 10% by weight of an organic acid addition salt of nicotine.

1 . A thin strip comprising:
 10 to 80% by weight of polyethylene oxide having a molecular weight of from 70,000 to 300,000 daltons;   5 to 50% by weight of a sugar alcohol having a melting point in excess of 75 EC;   5 to 30% by weight of polyethylene glycol having a molecular weight of from 100 to 4,000 daltons;   1 to 30% by weight of a carboxy vinyl polymer cross linked with an allyl ether of pentaerythritol; and   1 to 10% by weight of an organic acid addition salt of nicotine, wherein the thin strip is between 0.05 millimeters and 2.00 millimeters thick.   
     
     
         2 . The thin strip of  claim 1 , wherein the sugar alcohol comprises mannitol or sorbitol. 
     
     
         3 . The thin strip of  claim 1 , wherein the thin strip comprises:
 25 to 55% by weight of polyethylene oxide having a molecular weight of from 100,000 to 200,000 daltons;   35 to 45% by weight of a sugar alcohol having a melting point in excess of 150 EC;   7 to 15% by weight of polyethylene glycol having a molecular weight of from 300 to 600 daltons;   5 to 15% by weight of a carboxy vinyl polymer cross linked with an allyl ether of pentaerythritol; and   2 to 6% by weight of an organic acid addition salt of nicotine.   
     
     
         4 . The thin strip of  claim 1 , further comprising an alkaline buffer selected from the group consisting of: Potassium phosphate monobasic, sodium carbonate, sodium bicarbonate, sodium chloride, sodium phosphate dibasic and sodium phosphate monobasic. 
     
     
         5 . The thin strip  claim 1 , wherein the carboxy vinyl polymer cross linked an allyl ether of pentaerythritol is a polymer that is swellable in water. 
     
     
         6 . The thin strip of  claim 1 , wherein the carboxy vinyl polymer is cross linked with an allyl ether of pentaerythritol and has a glass transition temperature of between 100 EC and 110 EC in powder form. 
     
     
         7 . The thin strip of  claim 6 , Wherein the carboxy vinyl polymer is cross linked with an allyl ether of pentaerythritol and has a glass transition temperature of 105 EC in powder form. 
     
     
         8 . The thin strip of  claim 1 , wherein the carboxy vinyl polymer is cross linked with an allyl ether of pentaerythritol and has a viscosity of 29,400 to 39,400 centi-Poise measured at 25 EC. 
     
     
         9 . The thin strip of  claim 8 , wherein the thin strips comprises:
 40% by weight of polyethylene oxide having a molecular weight of 100,000 daltons;   40% by weight of mannitol;   10% by weight of polyethylene glycol having a molecular weight of 400 daltons;   5% by weight of a carboxy vinyl polymer wherein the carboxy vinyl polymer is cross linked with an allyl ether of pentaerythritol and has a viscosity of 29,400 to 39,400 centi-Poise measured at 25 EC;   4.34% by weight of nicotine bitartrate; and   0.66% by weight of potassium phosphate monobasic.   
     
     
         10 . The thin strip of  claim 1 , wherein the carboxy vinyl polymer is cross linked with an allyl ether of pentaerythritol and has a viscosity of 4,000 to 11,000 centi-Poise measured at 25 EC. 
     
     
         11 . A method of forming the thin strip of  claim 1 , the method comprising the steps of:
 (I) forming a composition comprising thin strip components of the polyethylene oxide, the sugar alcohol, the polyethylene glycol, the carboxy vinyl polymer, the organic acid addition salt of nicotine, and optionally the alkaline buffer of  claim 4 ,   (II) melt extruding a thin sheet having to a thickness of between 0.05 millimeters and 2.00 millimeters from the composition; and   (III) cutting the thin sheet into thin strips;   wherein the processing temperature during steps (I), (II), and (III) does not exceed the melting point temperature of the sugar alcohol.   
     
     
         12 . The method of  claim 11 , wherein the sugar alcohol comprises mannitol and the melt temperature during steps (I), (II), and (III) does not exceed 150 EC. 
     
     
         13 . The method of  claim 12 , wherein the sugar alcohol comprises sorbitol and the melt temperature during steps (I), (II), and (III) does not exceed 90 EC. 
     
     
         14 . The method of  claim 13 , wherein the melt temperature during steps (I), (II), and (III) does not exceed 80 EC. 
     
     
         15 . The method of  claim 14 , wherein the melt temperature during steps (I), (II), and (III) does not exceed 70 EC. 
     
     
         16 . The method of  claim 11 , wherein the thin strip is 0.1 to 0.8 millimeters thick. 
     
     
         17 . The method of  claim 11 , wherein the composition is formed in an extruder during hot melt extrusion step (II), wherein a portion of the organic acid addition salt of nicotine is introduced to the extruder in a downstream barrel from where other thin strip components are introduced. 
     
     
         18 . The method of  claim 11 , wherein steps (I), (II), and (III) are performed such that the thin strip has 1 to 8 mg of nicotine (free base equivalent). 
     
     
         19 . The method of  claim 18 , wherein steps (I), (II), and (III) are performed such that the thin strip has 2 mg or 4 mg of nicotine (free base equivalent). 
     
     
         20 . The method of  claim 11 , wherein the melt extruding step (II) further includes calendering the extrudate to the thickness of between 0.05 millimeters and 2.00 millimeters, or 0.1 to 0.8 millimeters of  claim 19 . 
     
     
         21 . A thin strip comprising:
 10 to 80% by weight of polyethylene oxide having a molecular weight of from 70,000 to 300,000 daltons;   5 to 50% by weight of a sugar alcohol having a melting point in excess of 75 EC;   5 to 30% by weight of polyethylene glycol having a molecular weight of from 100 to 4,000 daltons;   1 to 30% by weight of a carboxy vinyl polymer selected from the group consisting of a carboxy vinyl polymer cross linked with divinyl glycol or a carboxy vinyl polymer cross linked with an allyl ether of pentaerythritol; and   1 to 10% by weight of an active pharmaceutical ingredient adapted for transmucosal absorption into the blood stream, wherein the thin strip is between 0.05 millimeters and 2.00 millimeters thick.   
     
     
         22 . The thin strip of  claim 21 , wherein the carboxy vinyl polymer is a carboxy vinyl polymer cross linked with divinyl glycol and has a viscosity of 2,000 to 12,000 centi-Poise measured at 25 EC. 
     
     
         23 . The thin strip of  claim 21 , wherein the active pharmaceutical ingredient adapted for transmucosal absorption into the blood stream is an organic acid addition salt of nicotine.